Understanding how disease-causing bacteria control their genetic potential is crucial for the development of knowledge-led strategies to reduce the burden of food borne infections, and a major aim of the research in the Gut Health and Food Safety Programme of IFR.
The bacterial pathogen Campylobacter remains the most common cause of foodborne diarrhoeal disease in the UK and other developed countries. In the 2011-2012 annual report of the chief scientist of the Food Standards Agency, Campylobacter was responsible for more than half of the confirmed cases and hospital admissions in 2012 when compared with other major foodborne pathogens such as Salmonella, Listeria and E. coli. Similar data have been reported for other Western countries, such as in the recently reported European Food Safety update.
The chromosome of a bacterium contains all the genetic information that is required to make proteins and other building blocks, and is subject to intricate control mechanisms to ensure that specific features are only made when required and at the right levels. The need for such control mechanisms is essential for all living organisms, including humans. Understanding these mechanisms is an important step in devising control strategies ultimately aimed at lowering the burden of Campylobacter infection. One of the striking features of Campylobacter is that its chromosome is highly variable, both in gene content and gene order. This variation is thought to contribute to the success of Campylobacter as a pathogen, but such variability requires the bacterium to have both flexible and robust systems to ensure that genes are expressed when needed.
To understand how Campylobacter controls expression of its genetic potential, Dr Ida Porcelli and colleagues at the Institute of Food Research have produced a high-resolution map that shows the places in the Campylobacter chromosome from where genes are switched on. These so-called transcriptional start sites (TSS) have been mapped all over the chromosome, and this map is an important resource for Campylobacter researchers worldwide.
One of the surprising findings of the study is the large number of TSS, which was much higher than originally predicted. The information obtained can now be used to better predict how Campylobacter chromosomes can evolve and change without losing expression control of its genetic potential. In addition to this, several new potential genes and control mechanisms have been identified, and these are now being tested at IFR and in other laboratories worldwide.
The team at the IFR, led by Dr Arnoud van Vliet and funded by the Biotechnology and Biological Sciences Research Council, has used a high-throughput sequencing-based technique called Differential RNA Sequencing (dRNA-seq) to map the precise locations of the TSS, and have used this information to make predictions of how the control systems are continuously changing and evolving in related pathogenic and non-pathogenic bacteria, such as the human stomach bacterium Helicobacter pylori.
Dr. van Vliet commented “Mapping of the transcription start sites of the Campylobacter genes has been a great step forward in our understanding of how Campylobacter controls the expression of its genetic potential, and has also allowed the discovery of several new control mechanisms from Campylobacter. When we compare these with closely related bacteria like Helicobacter, we were amazed to see that they have no similar control mechanisms.. It almost seems like each of these bacteria just makes it up as they go along, rather than copying successfully used systems from elsewhere. That is an intriguing idea, and shows how flexible ,surprising and wonderfully interesting evolution can be!”
The work represents an important resource for future study into Campylobacter and related bacteria, and will contribute to our understanding of how this important food borne pathogen adapts and evolves.
This work has been published in BMC Genomics, and immediately received significant attention after its publication in September 2013, earning the BioMed “Highly Accessed” accolade within two weeks after publication, an honour that will stay with the paper. The paper also gets a 7 score from Altmetric, which puts the article in the top 25% of all articles ranked by attention.